This invention generally pertains to heterocyclic carbon compounds having drug and bio-affecting properties and to their preparation and use. In particular, the invention is concerned with a series of new 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives which are phosphodiesterase inhibitors, blood platelet antiaggregators and cardiotonic agents.
As a structural class, applicants are aware of relatively few 1,3-dihydro-2Himidazo[4,5-b]quinolin-2-ones with the following chemical literature illustrative of the art.
Kozak, et al., Bull. Intern. Acad. Polanaise, 1930A, 432-438 (Chem. Abs., 25, 5400) describes the unsubstituted compound 1,3-dihydro-2Himidazo[4,5-b]quinolin-2-one of formula (1). ##STR2##
Musial, Roczniki Chem., 1951, 25, 46-52 (Chem. Abs., 1953, 47, 4885f) synthesized 1,3-derivatives of (1) as illustrated in formula (2). ##STR3## R.sup.1 =Br, NO.sub.2, NH.sub.2 R.sup.2 =H, Br
Fryer, et al., J. Org. Chem., 1977, 42, 2212-2219 describes the 3,7,9-trisubstituted compound of formula (3). ##STR4##
Reid, et al., Chem. Ber., 1956, 89, 2684-2687 describes the synthesis of the 1,3-diphenyl derivative of formula (4). ##STR5##
No pharmacological utility is taught for the 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one structures disclosed in the aforementioned references which are of a chemical nature.
Various derivatives of the tetrahydroimidazo[2,1-b]quinozolin-2-one (5) heterocycle have been studied for their platelet inhibition and cardiotonic properties. ##STR6## For example:
Beverung, Jr., et al., U.S. Pat. No. 3,932,407 disclose a series of compounds useful as blood platelet antiaggregative and/or antihypertensive and/or bronchodilator agents of the tetrahydroimidazo[2,1-b]quinazolin-2-one class. Anagrelide (6), a particularly preferred member of the Beverung, Jr., et al. series, has been studied extensively, e.g., J. S. Fleming, et al., New Drugs Annual: Cardiovascular Drugs, Raven Press, pages 277-294, New York (1983). ##STR7##
Chodnekar, et al., U.S. Pat. No. 4,256,748 describes a series of compounds of the formula (7) as inhibitors of the aggregation of blood platelets and cardiotonic activity. ##STR8## Representative of the Chodneker compounds are RO 14-2525 (R.sup.4 =CH.sub.3, R.sup.3 =H, R.sup.2 =6-CH.sub.3, R.sup.1 =7-Br) and RO 13-6438 (R.sup.4 =CH.sub.3, R.sup.3 =H, R.sup.2 =6-CH.sub.3, R.sup.1 =H).